The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Joe Swift, Dennis E. Discher

    Research output: Contribution to journalArticlepeer-review

    Abstract

    How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage. © 2014. Published by The Company of Biologists Ltd.
    Original languageEnglish
    Pages (from-to)3005-3015
    Number of pages10
    JournalJournal of Cell Science
    Volume127
    Issue number14
    DOIs
    Publication statusPublished - 2014

    Keywords

    • Cell mechanics
    • Extra-cellular matrix
    • Mechanotransduction
    • Nucleoskeleton
    • Nucleus
    • Proteostasis

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